AQP4, Astrogenesis, and Hydrocephalus: A New Neurological Perspective

Aquaporin 4 (AQP4) is a cerebral glial marker that labels ependymal cells and astrocytes’ endfeet and is the main water channel responsible for the parenchymal fluid balance. However, in brain development, AQP4 is a marker of glial stem cells and plays a crucial role in the pathophysiology of pediatric hydrocephalus. Gliogenesis characterization has been hampered by a lack of biomarkers for precursor and intermediate stages and a deeper understanding of hydrocephalus etiology is needed. This manuscript is a focused review of the current research landscape on AQP4 as a possible biomarker for gliogenesis and its influence in pediatric hydrocephalus, emphasizing reactive astrogliosis. The goal is to understand brain development under hydrocephalic and normal physiologic conditions

THER-06. PROTEASOME INHIBITION IN PRIMARY MEDULLOBLASTOMA CELL CULTURE AND PATIENT-DERIVED XENOGRAFT MODELS: A POTENTIAL THERAPEUTIC IMPLICATION

Abstract Recent research has shown a role of proteasome ubiquitination in medulloblastoma tumorigenesis and proteasome inhibition as a possible therapeutic target. In medulloblastoma primary cell culture and in a Patched1 haploinsufficiency medulloblastoma mice model, bortezomib, a proteasome inhibitor, has been shown to limit tumor growth via induction of apoptosis and inhibition of cell proliferation. However, its clinical utility is limited by its inability to cross the blood brain barrier and association with peripheral neuropathy. Marizomib, a more lipophilic proteasome inhibitor, has been shown to cross the blood brain barrier in preclinical studies and is being used in Phase III studies for adult glioblastoma in combination with radiation and temozolomide. Here, we evaluated dose dependent cell killing of marizomib in two group 3, myc-amplified medulloblastoma cell cultures. IC50’s were determined and were consistent with and slightly lower than that seen in adult glioblastoma cell cultures. We suggest marizomib warrants further investigation as a potential therapeutic target for recurrent medulloblastoma. Future studies will include determination of IC50’s for marizomib in cell lines for all medulloblastoma molecular subgroups and primary cell cultures as well as in vitro testing with patient-derived xenograft models

Clonal analysis reveals nerve-dependent and independent roles on mammalian hind limb tissue maintenance and regeneration

The requirement and influence of the peripheral nervous system on tissue replacement in mammalian appendages remain largely undefined. To explore this question, we have performed genetic lineage tracing and clonal analysis of individual cells of mouse hind limb tissues devoid of nerve supply during regeneration of the digit tip, normal maintenance, and cutaneous wound healing. We show that cellular turnover, replacement, and cellular differentiation from presumed tissue stem/progenitor cells within hind limb tissues remain largely intact independent of nerve and nerve-derived factors. However, regenerated digit tips in the absence of nerves displayed patterning defects in bone and nail matrix. These nerve-dependent phenotypes mimic clinical observations of patients with nerve damage resulting from spinal cord injury and are of significant interest for translational medicine aimed at understanding the effects of nerves on etiologies of human injury

The impact of bilingualism on working memory in pediatric epilepsy

Impairments in executive skills broadly span across multiple childhood epilepsy syndromes and can adversely affect quality of life. Bilingualism has been previously shown to correlate with enhanced executive functioning in healthy individuals. This study sought to determine whether the bilingual advantage in executive functioning exists in the context of pediatric epilepsy. We retrospectively analyzed neuropsychological data in 52 children with epilepsy and compared executive function scores in monolingual versus bilingual children with epilepsy while controlling for socioeconomic status and ethnicity. Bilingual children performed significantly better on the Working Memory Index than did monolingual children. There were no significant differences on the remaining executive function variables. The bilingual advantage appears to persist for working memory in children with epilepsy. These findings suggest that bilingualism is potentially a protective variable in the face of epilepsy-related working memory dysfunction

The impact of bilingualism on working memory in pediatric epilepsy

Impairments in executive skills broadly span across multiple childhood epilepsy syndromes and can adversely affect quality of life. Bilingualism has been previously shown to correlate with enhanced executive functioning in healthy individuals. This study seeks to determine whether the bilingual advantage in executive functioning exists in the context of pediatric epilepsy. We retrospectively analyzed neuropsychological data in 52 children with epilepsy and compared executive function scores in monolingual versus bilingual children with epilepsy, while controlling for socioeconomic status and ethnicity. Bilingual children performed significantly better on the Working Memory scale than did monolingual children. There were no significant differences on the remaining executive function variables. The bilingual advantage appears to persist for working memory in children with epilepsy. These findings suggest that bilingualism is potentially a protective variable in the face of epilepsy-related working memory dysfunction